Selective serotonin reuptake inhibitors, SSRIs (typified by fluoxetine, fluvoxamine, paroxetine and sertraline) are used inter alia as antidepressants. In the following description reference will be made collectively to fluvoxamine when referring to SSRIs, except where otherwise stated.
Fluvoxamine maleate is a selective serotonin (5HT) reuptake inhibitor belonging to the 2-aminoethyl oxime ethers of aralkylketones chemical series. It is chemically designated as 5-methoxy-4′-(trifluoromethyl)valerophenone-(E)-O-(2-aminoethyl)oxime maleate (1:1) and has the empirical formula C15H21O2N2F3.C4H4O4. Fluvoxamine and other oxime ethers are disclosed in U.S. Pat. No. 4,085,225 (US Philips Corp.). Tablet, suppository and injection formulations are described.
Fluvoxamine has been shown to be effective in alleviating the symptoms of depression and in the treatment of obsessive compulsive disorder. It is conventionally administered in tablet form (25 mg, 50 mg and 100 mg) as fluvoxamine maleate sold under the Trade Mark Luvox (Solvay Pharmaceuticals Inc.). Conventional fluvoxamine therapy typically starts with 50 mg administered as a single dose at bedtime. The dosage may be gradually increased in 50 mg increments every 4 to 7 days, as tolerated, until maximum therapeutic benefit is achieved, not to exceed 300 mg per day. It is advisable that a total daily dose of more than 100 mg should be given in two divided doses. If the doses are not equal, the larger dose is typically given at bedtime.
Fluvoxamine is extensively metabolised by the liver and excreted by the kidneys in urine. Luvox® is subject to extensive first pass effect, typically giving an absolute bioavailability of about 53%. Typically single oral doses of Luvox® result in peak plasma levels 3 to 8 hours after administration. The plasma elimination half-life of fluvoxamine at steady state after multiple oral doses of 100 mg/day in healthy, young volunteers is reported to be 15.6 hours.
As stated above, conventional fluvoxamine tablets are currently titrated gradually to a tolerated dose with maximum therapeutic benefit, with doses of greater than 100 mg given in two divided doses. The gradual titration and adverse events related to conventional once-daily dosing of doses greater than 100 mg may reduce patent compliance and delay the onset of therapeutic benefit.
It is an object of the present invention therefore to provide a controlled release selective serotonin (5HT) reuptake inhibitor formulation.
It is another object of the present invention to provide a controlled release SSRI formulation suitable for administration no more frequently on the average than at twelve hour intervals.
It is another object of the present invention to provide a controlled release SSRI formulation suitable for once or twice daily administration.
A further object of the present invention is to provide a method of treatment of depression and/or obsessive compulsive disorder.